Publications by authors named "Lobat Tayebi"

131 Publications

Highly selective magnetic dual template molecularly imprinted polymer for simultaneous enrichment of sulfadiazine and sulfathiazole from milk samples based on syringe-to-syringe magnetic solid-phase microextraction.

Talanta 2021 Sep 28;232:122449. Epub 2021 Apr 28.

Marquette University School of Dentistry, Milwaukee, WI, USA. Electronic address:

Antibiotics, such as sulfadiazine and sulfathiazole, are widely used in veterinary applications which can result in remains in edible animal products. Therefore, there is an immense need for a reliable, selective, sensitive, and simple analytical technique for monitoring the concentration of sulfadiazine (SDZ) and sulfathiazole (STZ) in edible animal products. In this regard, we developed a magnetic dual template molecularly imprinted polymer (MMIP) to determine the SDZ and STZ in milk samples. For the sensitive and selective extraction and determination of target analytes, MMIPs have been combined with the syringe-to-syringe magnetic solid-phase microextraction (SS-MSPME) method. In addition, we used central composite design (CCD) for the extraction of SDZ and STZ. With optimum conditions, an efficient, rapid, and convenient technique for the preconcentration and determination of SDZ and STZ in milk samples by SS-MSPME coupling with HPLC-UV was developed. Using our combined approach, the limits of detection are 0.9 and 1.3 ng mL for SDZ and STZ, respectively, along with good linearity and determination coefficients higher than 0.98. Our method demonstrates a practical approach for the deduction of antibiotics in milk samples with high recoveries and selectivity.
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http://dx.doi.org/10.1016/j.talanta.2021.122449DOI Listing
September 2021

Vascularization strategies in tissue engineering approaches for soft tissue repair.

J Tissue Eng Regen Med 2021 May 24. Epub 2021 May 24.

Marquette University School of Dentistry, Milwaukee, WI, USA.

Insufficient vascularization during tissue repair is often associated with poor clinical outcomes. This is a concern especially when patients have critical-sized injuries, where the size of the defect restricts vascularity, or even in small defects that have to be treated under special conditions, such as after radiation therapy (relevant to tumor resection) that hinders vascularity. In fact, poor vascularization is one of the major obstacles for clinical application of tissue engineering methods in soft tissue repair. As a key issue, lack of graft integration, caused by inadequate vascularization after implantation, can lead to graft failure. Moreover, poor vascularization compromises the viability of cells seeded in deep portions of scaffolds/graft materials, due to hypoxia and insufficient nutrient supply. In this article we aim to review vascularization strategies employed in tissue engineering techniques to repair soft tissues. For this purpose, we start by providing a brief overview of the main events during the physiological wound healing process in soft tissues. Then, we discuss how tissue repair can be achieved through tissue engineering, and considerations with regards to the choice of scaffold materials, culture conditions, and vascularization techniques. Next, we highlight the importance of vascularization, along with strategies and methods of prevascularization of soft tissue equivalents, particularly cell-based prevascularization. Lastly, we present a summary of commonly used in vitro methods during the vascularization of tissue-engineered soft tissue constructs.
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http://dx.doi.org/10.1002/term.3225DOI Listing
May 2021

Impact of Lipid/Magnesium Hydroxide Hybrid Nanoparticles on the Stability of Vascular Endothelial Growth Factor-Loaded PLGA Microspheres.

ACS Appl Mater Interfaces 2021 Jun 18;13(21):24370-24384. Epub 2021 May 18.

Marquette University School of Dentistry, Milwaukee, Wisconsin 53201-1881, United States.

The purpose of the present study is to characterize poly(d,l-lactide--glycolide) (PLGA) composite microcarriers for vascular endothelial growth factor (VEGF) delivery. To reduce the initial burst release and protect the bioactivity, VEGF is encapsulated in soybean l-α-phosphatidylethanolamine (PE) and l-α-phosphatidylcholine (PC) anhydrous reverse micelle (VEGF-RM) nanoparticles. Also, mesoporous nano-hexagonal Mg(OH) nanostructure (MNS)-loaded PE/PC anhydrous reverse micelle (MNS-RM) nanoparticles are synthesized to suppress the induced inflammation of PLGA acidic byproducts and regulate the release profile. The flow-focusing microfluidic geometry platforms are used to fabricate different combinations of PLGA composite microspheres (PLGA-CMPs) with MNSs, MNS-RM, VEGF-RM, and native VEGF. The essential parameters of each formulation, such as release profiles, encapsulation efficacy, bioactivity, inflammatory response, and cytotoxicity, are investigated by in vitro and in vivo studies. The results indicate that generated acidic byproducts during the hydrolytic degradation process of PLGA can be buffered, and pH values inside and outside microspheres can remain steady during degradation by MNSs. Furthermore, the significant improvement in the stability of the encapsulated VEGF is confirmed by the bioactivity assay. In vitro release study shows that the VEGF initial burst release is well minimized in the present microcarriers. The present monodisperse PLGA-CMPs can be widely used in various tissue engineering and therapeutic applications.
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http://dx.doi.org/10.1021/acsami.0c22140DOI Listing
June 2021

Molecular insight into optimizing the N- and P-doped fullerenes for urea removal in wearable artificial kidneys.

J Mater Sci Mater Med 2021 Apr 23;32(5):49. Epub 2021 Apr 23.

Marquette University School of Dentistry, Milwaukee, WI, 53233, USA.

Urea is the result of the breakdown of proteins in the liver, the excess of which circulates in the blood and is adsorbed by the kidneys. However, in the case of kidney diseases, some products, specifically urea, cannot be removed from the blood by the kidneys and causes serious health problems. The end-stage renal disease (ESRD) patients are not able to purify their blood, which endangers their life. ESRD patients require dialysis, a costly and difficult method of urea removal from the blood. Wearable artificial kidneys (WAKs) are consequently designed to remove the waste from blood. Regarding the great amount of daily urea production in the body, WAKs should contain strong and selective urea adsorbents. Fullerenes-which possess fascinating chemical properties-have been considered herein to develop novel urea removal adsorbents. Molecular dynamics (MD) has enabled researchers to study the interaction of different materials and can pave the way toward facilitating the development of wearable devices. In this study, urea adsorption by N-doped fullerenes and P-doped fullerenes were assessed through MD simulations. The urea adsorption was simulated by five samples of fullerenes, with phosphorous and different nitrogen dopant contents. For comparing the urea adsorption capacity in the performed simulations, detailed characteristics-including the energy analysis, radius of gyration, radial distribution function (RDF), root-mean-square fluctuation (RMSD), and H-bond analyses were investigated. It had been determined that the fullerene containing 8% nitrogen-with the highest reduction in the radius of gyration, the maximum RDF, a high adsorption energy, and a high number of hydrogen bonds-adsorbs urea more efficiently.
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http://dx.doi.org/10.1007/s10856-021-06525-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065003PMC
April 2021

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Promising Treatment for COVID-19 Pandemic.

Exp Clin Transplant 2021 Feb 23. Epub 2021 Feb 23.

From the Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

The pandemic of severe acute respiratory syndrome coronavirus-2 infection has prompted the urgent need for novel therapeutic approaches, especially for patients in critically severe conditions. To date, the pathogenesis of COVID-19 is not completely understood, and finding an effective new drug is still inconclusive. Mesenchymal stromal cell-derived extracellular vesicles contain large amounts of proteins, messenger RNA, and microRNAs that act as vehicles that transfer the cargo between cells. These nanotherapeutic materials exert anti-inflammatory effects on the immune system, which are necessary for subsidence of acute inflammation and promotion of tissue repair and regeneration. Therefore, the consideration of mesenchymal stromal cell-derived extracellular vesicles as a new, safe, and effective therapeutic approach in the treatment of COVID-19 pneumonia is suggested.
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http://dx.doi.org/10.6002/ect.2020.0296DOI Listing
February 2021

Comparison of osteogenic differentiation potential of induced pluripotent stem cells and buccal fat pad stem cells on 3D-printed HA/β-TCP collagen-coated scaffolds.

Cell Tissue Res 2021 May 12;384(2):403-421. Epub 2021 Jan 12.

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Production of a 3D bone construct with high-yield differentiated cells using an appropriate cell source provides a reliable strategy for different purposes such as therapeutic screening of the drugs. Although adult stem cells can be a good source, their application is limited due to invasive procedure of their isolation and low yield of differentiation. Patient-specific human-induced pluripotent stem cells (hiPSCs) can be an alternative due to their long-term self-renewal capacity and pluripotency after several passages, resolving the requirement of a large number of progenitor cells. In this study, a new biphasic 3D-printed collagen-coated HA/β-TCP scaffold was fabricated to provide a 3D environment for the cells. The fabricated scaffolds were characterized by the 3D laser scanning digital microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and mechanical test. Then, the osteogenesis potential of the hiPSC-seeded scaffolds was investigated compared to the buccal fat pad stem cell (BFPSC)-seeded scaffolds through in vitro and in vivo studies. In vitro results demonstrated up-regulated expressions of osteogenesis-related genes of RUNX2, ALP, BMP2, and COL1 compared to the BFPSC-seeded scaffolds. In vivo results on calvarial defects in the rats confirmed a higher bone formation in the hiPSC-seeded scaffolds compared to the BFPSC-seeded groups. The immunofluorescence assay also showed higher expression levels of collagen I and osteocalcin proteins in the hiPSC-seeded scaffolds. It can be concluded that using the hiPSC-seeded scaffolds can lead to a high yield of osteogenesis, and the hiPSCs can be used as a superior stem cell source compared to BFPSCs for bone-like construct bioengineering.
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http://dx.doi.org/10.1007/s00441-020-03374-8DOI Listing
May 2021

Biomaterials in Valvular Heart Diseases.

Front Bioeng Biotechnol 2020 9;8:529244. Epub 2020 Dec 9.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Valvular heart disease (VHD) occurs as the result of valvular malfunction, which can greatly reduce patient's quality of life and if left untreated may lead to death. Different treatment regiments are available for management of this defect, which can be helpful in reducing the symptoms. The global commitment to reduce VHD-related mortality rates has enhanced the need for new therapeutic approaches. During the past decade, development of innovative pharmacological and surgical approaches have dramatically improved the quality of life for VHD patients, yet the search for low cost, more effective, and less invasive approaches is ongoing. The gold standard approach for VHD management is to replace or repair the injured valvular tissue with natural or synthetic biomaterials. Application of these biomaterials for cardiac valve regeneration and repair holds a great promise for treatment of this type of heart disease. The focus of the present review is the current use of different types of biomaterials in treatment of valvular heart diseases.
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http://dx.doi.org/10.3389/fbioe.2020.529244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793990PMC
December 2020

The colorful world of carotenoids: a profound insight on therapeutics and recent trends in nano delivery systems.

Crit Rev Food Sci Nutr 2021 Jan 5:1-40. Epub 2021 Jan 5.

Department of Chemical Engineering, Northeastern University, Boston, MA, USA.

The therapeutic effects of carotenoids as dietary supplements to control or even treat some specific diseases including diabetic retinopathy, cardiovascular diseases, bacterial infections, as well as breast, prostate, and skin cancer are discussed in this review and also thoughts on future research for their widespread use are emphasized. From the stability standpoint, carotenoids have low bioavailability and bioaccessibility owing to their poor water solubility, deterioration in the presence of environmental stresses such as oxygen, light, and high heat as well as rapid degradation during digestion. Nanoencapsulation technologies as wall or encapsulation materials have been increasingly used for improving food product functionality. Nanoencapsulation is a versatile process employed for the protection, entrapment, and the delivery of food bioactive products including carotenoids from diverse environmental conditions for extended shelf lives and for providing controlled release. Therefore, we present here, recent (mostly during the last five years) nanoencapsulation methods of carotenoids with various nanocarriers. To us, this review can be considered as the first highlighting not only the potential therapeutic effects of carotenoids on various diseases but also their most effective nanodelivery systems.HighlightsBioactive compounds are of deep interest to improve food properties.Carotenoids (such as β-carotene and xanthophylls) play indispensable roles in maintaining human health and well-being.A substantial research effort has been carried out on developing beneficial nanodelivery systems for various carotenoids.Nanoencapsulation of carotenoids can enhance their functional properties.Stable nanoencapsulated carotenoids could be utilized in food products.
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http://dx.doi.org/10.1080/10408398.2020.1867958DOI Listing
January 2021

A new phantom to evaluate the tissue dissolution ability of endodontic irrigants and activating devices.

Restor Dent Endod 2020 Nov 24;45(4):e45. Epub 2020 Aug 24.

Marquette University School of Dentistry, Milwaukee, WI, USA.

Objective: The aim of this study was to introduce a gelatin/bovine serum albumin (BSA) tissue standard, which provides dissolution properties identical to those of biological tissues. Further, the study evaluated whether the utilization of endodontic activating devices led to enhanced phantom dissolution rates.

Materials And Methods: Bovine pulp tissue was obtained to determine a benchmark of tissue dissolution. The surface area and mass of samples were held constant while the ratio of gelatin and BSA were varied, ranging from 7.5% to 10% gelatin and 5% BSA. Each sample was placed in an individual test tube that was filled with an appropriate sodium hypochlorite solution for 1, 3, and 5 minutes, and then removed from the solution, blotted dry, and weighed again. The remaining tissue was calculated as the percent of initial tissue to determine the tissue dissolution rate. A radiopaque agent (sodium diatrizoate) and a fluorescent dye (methylene blue) were added to the phantom to allow easy quantification of phantom dissolution in a canal block model when activated using ultrasonic (EndoUltra) or sonic (EndoActivator) energy.

Results: The 9% gelatin + 5% BSA phantom showed statistically equivalent dissolution to bovine pulp tissue at all time intervals. Furthermore, the EndoUltra yielded significantly more phantom dissolution in the canal block than the EndoActivator or syringe irrigation.

Conclusions: Our phantom is comparable to biological tissue in terms of tissue dissolution and could be utilized for tests due to its injectability and detectability.
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http://dx.doi.org/10.5395/rde.2020.45.e45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691255PMC
November 2020

Simultaneous selective enrichment of methylparaben, propylparaben, and butylparaben from cosmetics samples based on syringe-to-syringe magnetic fluid phase microextraction.

Talanta 2021 Jan 1;221:121547. Epub 2020 Sep 1.

Marquette University School of Dentistry, Milwaukee, WI, 53233, USA.

Present work is the preparation of novel magnetic nanofluids based on deep eutectic solvent and used for the rapid microextraction of methylparaben (MP), propylparaben (PP), and butylparaben (BP) from cosmetics samples using syringe-to-syringe dispersive magnetic nanofluid microextraction procedure (SS-DMNF-ME). The optimization of the extraction of MP, PP, and BP was performed through central composite design (CCD). The optimum extraction conditions were assessed by optimizing pH, nanofluid volume, NaCl concentration, cycle number, and methanol volume. pH 8.0, 200 μL of magnetic nanofluid, 6% w/v of NaCl, eight cycles of injection/back injection, and 80 μL of methanol were the optimum extraction conditions, with the maximum recoveries of 98.62%, 100.92%, and 99.13% for MP, PP, and BP, respectively. The figures of merit calculated under the optimum condition were achieved from the CCD, and the developed method exhibited the low limits of quantitation (4.3, 3.0, and 2.7 ng mL) and detection (1.3, 0.9, and 0.8 ng mL) for MP, PP, and BP, respectively, as well as excellent linearity with R > 0.99. The relative recoveries of three parabens in the actual samples were 85.99-99.07% with relative standard deviations ≤5.52%. In comparison to other extraction methods, SS-DMNF-ME was readily and rapidly determined MP, PP, and BP using HPLC-UV, and experimental data showed the efficiency, robustness, and reliability of the proposed method.
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http://dx.doi.org/10.1016/j.talanta.2020.121547DOI Listing
January 2021

A Review on the Biodistribution, Pharmacokinetics and Toxicity of Bismuth-Based Nanomaterials.

Int J Nanomedicine 2020 25;15:7079-7096. Epub 2020 Sep 25.

Marquette University School of Dentistry, Milwaukee, WI 53233, USA.

Here, bismuth-based nanomaterials (Bi-based NMs) are introduced as promising theranostic agents to enhance image contrast as well as for the therapeutic gain for numerous diseases. However, understanding the interaction of such novel developed nanoparticles (NPs) within a biological environment is a requisite for the translation of any promising agent from the lab bench to the clinic. This interaction delineates the fate of NPs after circulation in the body. In an ideal setting, a nano-based therapeutic agent should be eliminated via the renal clearance pathway, meanwhile it should have specific targeting to a diseased organ to reach an effective dose and also to overcome off-targeting. Due to their clearance pathway, biodistribution patterns and pharmacokinetics (PK), Bi-based NMs have been found to play a determinative role to pass clinical approval and they have been investigated extensively in vivo to date. In this review, we expansively discuss the possible toxicity induced by Bi-based NMs on cells or organs, as well as biodistribution profiles, PK and the clearance pathways in animal models. A low cytotoxicity of Bi-based NMs has been found in vitro and in vivo, and along with their long-term biodistribution and proper renal clearance in animal models, the translation of Bi-based NMs to the clinic as a useful novel theranostic agent is promising to improve numerous medical applications.
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http://dx.doi.org/10.2147/IJN.S250001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526011PMC
December 2020

A tri-component knee plug for the 3rd generation of autologous chondrocyte implantation.

Sci Rep 2020 10 12;10(1):17048. Epub 2020 Oct 12.

Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, OX3 7DQ, UK.

Here, we report a newly designed knee plug to be used in the 3rd generation of Autologous Chondrocyte Implantation (ACI) in order to heal the damaged knee cartilage. It is composed of three components: The first component (Bone Portion) is a 3D printed hard scaffold with large pores (~ 850 µm), made by hydroxyapatite and β-tricalcium phosphate to accommodate the bony parts underneath the knee cartilage. It is a cylinder with a diameter of 20 mm and height of 7.5 mm, with a slight dome shape on top. The plug also comprises a Cartilage Portion (component 2) which is a 3D printed gelatin/elastin/sodium-hyaluronate soft thick porous membrane with large pores to accommodate chondrocytes. Cartilage Portion is secured on top of the Bone Portion using mechanical interlocking by designing specific knobs in the 3D printed construct of the Cartilage Portion. The third component of the plug (Film) is a stitchable permeable membrane consisting of polycaprolactone (PCL) on top of the Cartilage Portion to facilitate sliding of the knee joint and to hold the entire plug in place while allowing nutrients delivery to the Cartilage Portion. The PCL Film is prepared using a combination of film casting and sacrificial material leaching with a pore size of 10 µm. It is surface modified to have specific affinity with the Cartilage Portion. The detailed design criteria and production process of this plug is presented in this report. Full in vitro analyses have been performed, which indicate the compatibility of the different components of the plug relative to their expected functions.
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http://dx.doi.org/10.1038/s41598-020-73863-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550599PMC
October 2020

3D construct of hydroxyapatite/zinc oxide/palladium nanocomposite scaffold for bone tissue engineering.

J Mater Sci Mater Med 2020 Sep 30;31(10):85. Epub 2020 Sep 30.

Marquette University School of Dentistry, Milwaukee, WI, 53233, USA.

The purpose of this study was to produce and characterize Hydroxyapatite/Zinc Oxide/Palladium (HA/0.05 wt% ZnO/0.1 wt% Pd) nanocomposite scaffolds and study their mechanical and antibacterial properties, biocompatibility and bioactivity. The initial materials were developed using sol-gel and precipitation methods. Scaffolds were characterized using atomic absorption analysis (AA), scanning electron microcopy (SEM), energy dispersive spectroscopy (EDS) and transmission electron microscopy (TEM), atomic force microscopy (AFM) and Brunauer-EmmeS-Teller (BET) method. Furthermore, the bioactivity of scaffolds in simulated body fluid (SBF) and the interaction of dental pulp stem cells (DPSCs) with the nanocomposite scaffolds were assessed. Our results showed that the HA/ZnO/Pd (H1), HA/ZnO/Pd coated by 0.125 g chitosan (H2) and HA/ZnO/Pd coated by 0.25 g chitosan (H3) scaffolds possess higher compressive strength and toughness and lower microhardness and density compared to the pure HA (H0) scaffolds. Immersion of samples in SBF showed the deposition of apatite on the surface of the scaffolds. The biocompatibility assay indicated lower cell proliferation on the H1, H2 and H3 in comparison to the H0. The antibacterial results obtained show a significant impact by loading Pd/ZnO on HA in the deactivation of microorganisms in vitro.
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http://dx.doi.org/10.1007/s10856-020-06409-2DOI Listing
September 2020

Shedding light on the role of keratinocyte-derived extracellular vesicles on skin-homing cells.

Stem Cell Res Ther 2020 09 29;11(1):421. Epub 2020 Sep 29.

Marquette University School of Dentistry, Milwaukee, WI, 53233, USA.

Extracellular vesicles (EVs) are secretory lipid membranes with the ability to regulate cellular functions by exchanging biological components between different cells. Resident skin cells such as keratinocytes, fibroblasts, melanocytes, and inflammatory cells can secrete different types of EVs depending on their biological state. These vesicles can influence the physiological properties and pathological processes of skin, such as pigmentation, cutaneous immunity, and wound healing. Since keratinocytes constitute the majority of skin cells, secreted EVs from these cells may alter the pathophysiological behavior of other skin cells. This paper reviews the contents of keratinocyte-derived EVs and their impact on fibroblasts, melanocytes, and immune cells to provide an insight for better understanding of the pathophysiological mechanisms of skin disorders and their use in related therapeutic approaches.
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http://dx.doi.org/10.1186/s13287-020-01929-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523352PMC
September 2020

Recent developments in targeting genes and pathways by RNAi-based approaches in colorectal cancer.

Med Res Rev 2021 01 29;41(1):395-434. Epub 2020 Sep 29.

Marquette University School of Dentistry, Milwaukee, Wisconsin, USA.

A wide spectrum of genetic and epigenetic variations together with environmental factors has made colorectal cancer (CRC), which involves the colon and rectum, a challenging and heterogeneous cancer. CRC cannot be effectively overcomed by common conventional therapies including surgery, chemotherapy, targeted therapy, and hormone replacement which highlights the need for a rational design of novel anticancer therapy. Accumulating evidence indicates that RNA interference (RNAi) could be an important avenue to generate great therapeutic efficacy for CRC by targeting genes that are responsible for the viability, cell cycle, proliferation, apoptosis, differentiation, metastasis, and invasion of CRC cells. In this review, we underline the documented benefits of small interfering RNAs and short hairpin RNAs to target genes and signaling pathways related to CRC tumorigenesis. We address the synergistic effects of RNAi-mediated gene knockdown and inhibitors/chemotherapy agents to increase the sensitivity of CRC cells to common therapies. Finally, this review points new delivery systems/materials for improving the cellular uptake efficiency and reducing off-target effects of RNAi.
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http://dx.doi.org/10.1002/med.21735DOI Listing
January 2021

Green Synthesis of ZnO NPs via : Evaluation of Potential Antioxidant, Antibacterial, Mammalian Cell Viability, H1N1 Influenza Virus Inhibition and Photocatalytic Activities.

J Biomed Nanotechnol 2020 Apr;16(4):456-466

Among different forms of metallic nanoparticles (NPs), zinc oxide (ZnO) NPs with a very special bandgap of 3.37 eV and considerable binding energy of excitation (60 meV at room temperature), have been classified as high-tech nanoparticles. This study aimed to synthesize ZnO NPs using the extract from leaves. The synthesized nanoparticles were fully characterized and the photocatalytic activity was evaluated through the degradation of methylene blue. Additionally, the potential biological activities of such ZnO NPs in terms of their antibacterial activity were determined, as well as their antioxidant (30 minutes), antiviral (48 hours) and mammalian cell viability properties (48 and 72 hours). This study is the first investigation into the synthesis of such green ZnO NPs mediated by this plant extract, in which both photocatalytic and biomedical properties were found to be promising. The IC50 values for the antibacterial activities were found to be around 17.4 g mL and 28.5 g mL for and , respectively, and the antioxidant activity was comparable with the standard BHT. However, the H1N1 inhibition rate using the present green ZnO NPs was lower than oseltamivir (up to about 40% for ZnO NPs and above 90% for oseltamivir) which was expected since it is a drug, but was higher than many synthetic nanoparticles reported in the literature. In addition, the mammalian cell viability assay showed a higher than 80% cellular viability in the presence of 5, 10 and 20 g mL nanoparticles, and showed a higher than 50% cellular viability in the presence of 50 and 75 g mL nanoparticles. In this manner, this study showed that these green ZnO NPs should be studied for a wide range of medical applications.
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http://dx.doi.org/10.1166/jbn.2020.2916DOI Listing
April 2020

Fibroblast encapsulation in gelatin methacryloyl (GelMA) versus collagen hydrogel as substrates for oral mucosa tissue engineering.

J Oral Biol Craniofac Res 2020 Oct-Dec;10(4):573-577. Epub 2020 Aug 25.

School of Dentistry, Marquette University, Milwaukee, WI, 53233, USA.

Purpose: Over the past decades, a variety of biomaterials have been investigated in terms of their suitability for oral mucosa tissue engineering. The aim of this study was to compare collagen and GelMA hydrogels as connective tissue scaffolds for fibroblasts and as substrates for seeding and culture of oral epithelial keratinocyte cells.

Methods: Human primary oral fibroblast and keratinocyte cells were isolated from gingival biopsies. The mixture of fibroblasts with GelMA or collagen gel were aliquoted within six-well tissue culture plate inserts and cross-linked using visible light or reconstitution buffer/heat, respectively. The viability of fibroblasts in the hydrogels was investigated after one and three days of cultivation using the PrestoBlue assay. Following the addition and culture of oral keratinocytes onto the connective tissue constructs, the tissue-engineered oral mucosa was assessed histologically.

Results: The tissue viability assay shows that collagen hydrogels encapsulating fibroblasts displayed significantly higher cell viability than cell-laden GelMA constructs after 24 and 72 h ( < 0.05). A stratified and differentiated epithelium has formed on the surface of cell-laden collagen hydrogel but not on the surface of the GelMA-based substrate.

Conclusion: Collagen-based scaffold offers superior biological properties compared to GelMA hydrogel in terms of oral fibroblast growth, as well as epithelial cell adhesion and differentiation. Therefore, collagen-based hydrogels remain the preferred choice for oral mucosa tissue engineering.
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http://dx.doi.org/10.1016/j.jobcr.2020.08.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479286PMC
August 2020

Synthesis of novel reducing agent for formation of metronidazole-capped silver nanoparticle and evaluating antibacterial efficiency in gram-positive and gram-negative bacteria.

Heliyon 2020 Aug 28;6(8):e04747. Epub 2020 Aug 28.

School of Dentistry, Marquette University, Milwaukee, USA.

In this study, a new type of silver nanoparticles capped with metronidazolium based ionic liquid is synthesized. By this aim, metronidazole is altered to ionic-liquid type structure with citrate counter ion as reducing agent. The produced reducing agent was characterized using HNMR and CNMR and FT-IR. The capability of metronidazolium-based reducing agent in formation and capping silver nanoparticles was examined in a chemical reaction. More specifically, synthesized silver nanoparticles were synthesized and capped with metronidazolium-citrate based ionic liquid, while the formation of particles in 48 h was monitored by UV-Vis spectroscopy. Fourier transform infrared spectroscopy showed the presence of capping agents around silver nanoparticles. The amount of metronidazolium and citrate as capping agents was determined by thermal gravimetric analysis. The prepared crystalline structure of silver nanoparticles was proved by X-ray diffraction spectroscopy. PSA analysis and TEM was performed to determine the size of particles. The synthesized silver nanoparticle has the potential to be used as an antibacterial agent in preparation of wound dressing with extra capability and efficacy in aerobic and anaerobic bacterium. In this regard, the antibacterial efficacy of discs from different concentration of silver nanoparticles in calcium alginate medium were evaluated in Gram-negative and Gram-positive bacterium.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472853PMC
August 2020

Recent Advances in Designing 5-Fluorouracil Delivery Systems: A Stepping Stone in the Safe Treatment of Colorectal Cancer.

Int J Nanomedicine 2020 30;15:5445-5458. Epub 2020 Jul 30.

Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

5-Fluorouracil (5-FU) has become one of the most widely employed antimetabolite chemotherapeutic agents in recent decades. It is considered a first line antineoplastic agent for the treatment of colorectal cancer. Unfortunately, chemotherapy with 5-FU has several limitations, including its short half-life, high cytotoxicity and low bioavailability. In order to overcome the drawbacks of 5-FU and enhance its therapeutic efficiency, many scientific groups have focused on designing a new delivery system to successfully deliver 5-FU to tumor sites. We provide a comprehensive review on different strategies to design effective delivery systems, including nanoformulations, drug-conjugate formulations and other strategies for the delivery of 5-FU to colorectal cancer. Furthermore, co-delivery of 5-FU with other therapeutics is discussed. This review critically highlights the recent innovations in and literature on various types of carrier system for 5-FU.
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http://dx.doi.org/10.2147/IJN.S257700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398750PMC
October 2020

Graphite/gold nanoparticles electrode for direct protein attachment: characterization and gas sensing application.

Environ Sci Pollut Res Int 2020 Dec 30;27(34):43202-43211. Epub 2020 Jul 30.

Department of Developmental Sciences, Marquette University School of Dentistry, Milwaukee, WI, 53233, USA.

In this work, graphite/gold nanoparticles (G/AuNPs) were synthesized through a facile chemical method, and its potential application for direct protein attachment for electrochemical detection of carbon monoxide (CO) was investigated. The preparation of G/AuNPs electrodes was optimized by synthesizing the nanoparticles in different concentration of HAuCl.3HO at various temperatures. The G/AuNPs electrode was subsequently modified by four types of mercaptopropionic acid, including 1-mercaptopropionic, 3-mercaptopropionic, 6-mercaptopropionic, and 11-mercaptopropionic acid, to achieve the best structure for protein attachment. Visible absorption and electrochemical studies showed that 3-mercaptopropionic acid possesses the best performance regarding the electrical conductivity between electrode and protein redox center. The cyclic voltammetry results revealed that the modified electrode has an appropriate performance for CO detection at very low concentrations while keeping a linear response. The limit of detection for the modified electrode was calculated to be about 0.2 ppb. Finally, the interactions of cytochrome C and carbon monoxides were simulated using molecular dynamics (MD), and the effect of protein conformation changes on the electrochemical signal was thoroughly examined. The simulation results suggested that the proposed electrochemical sensor has an acceptable performance for the detection of CO due to less fluctuation of amino acids near the protein chain in the presence of CO molecules.
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http://dx.doi.org/10.1007/s11356-020-10286-1DOI Listing
December 2020

Aptamer-conjugated PLGA nanoparticles for delivery and imaging of cancer therapeutic drugs.

Arch Biochem Biophys 2020 09 24;691:108485. Epub 2020 Jul 24.

Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

Most problems associated with chemotherapeutic agents involve non-specific cytotoxicity, low intratumoral accumulation and drug resistance. Targeted drug delivery systems (TDDS) based on nanoparticles (NPs) are a new strategy for better therapeutic efficiency, along with reduction of side effects commonly seen with cancer drugs. Poly (lactic-co-glycolic acid) (PLGA), as one of the furthest developed synthetic polymer, has gained significant attention because of excellent properties-including biodegradability and biocompatibility, controlled release of drug, protection of drug or gene from decomposition and ability to modify surface with targeting agents for both cancer diagnosis and therapy. Aptamers are single-stranded RNA or DNA that can fold through intramolecular interactions into specific three-dimensional structures to selectively and exclusively bind with interested biomarkers. In this review, we explain the latest developments regarding the application of aptamer-decorated PLGA NPs in delivery of therapeutic agents or cancer-related genes into cancer cells. Additionally, we discuss the most recent efforts in the field of aptamer-grafted PLGA-based NPs as theranostics and stimuli-responsive agents.
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http://dx.doi.org/10.1016/j.abb.2020.108485DOI Listing
September 2020

Microfluidic fabrication of microcarriers with sequential delivery of VEGF and BMP-2 for bone regeneration.

Sci Rep 2020 07 16;10(1):11764. Epub 2020 Jul 16.

Marquette University School of Dentistry, Milwaukee, WI, USA.

Wound instability and poor functional vascularization in bone tissue engineering lead to lack of tissue integration and ultimate failure of engineered grafts. In order to harness the regenerative potential of growth factors and stimulate bone healing, present study aims to design multifunctional cell therapy microcarriers with the capability of sequential delivery of essential growth factors, bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF). An on-chip double emulsion method was implemented to generate monodisperse VEGF encapsulated microcarriers. Bio-inspired poly(3,4-dihydroxyphenethylamine) (PDA) was then functionalized to the microcarriers surface for BMP-2 conjugation. The microcarriers were seeded with mesenchymal stem cells (MSCs) using a dynamic culture technique for cells expansion. Finally, the microcarriers were incorporated into an injectable alginate-RGD hydrogel laden with endothelial cells (ECs) for further analysis. The DNA and calcium content, as well as ALP activity of the construct were analyzed. The confocal fluorescent microscopy was employed to monitor the MSCs and tunneling structure of ECs. Eventually, the capability of developed microcarriers for bone tissue formation was examined in vivo. Microfluidic platform generated monodisperse VEGF-loaded PLGA microcarriers with size-dependent release patterns. Microcarriers generated with the on-chip technique showed more sustained VEGF release profiles compared to the conventional bulk mixing method. The PDA functionalization of microcarriers surface not only provided immobilization of BMP-2 with prolonged bioavailability, but also enhanced the attachment and proliferation of MSCs. Dynamic culturing of microcarriers showcased their great potential to boost MSCs population required for stem cell therapy of bone defects. ALP activity and calcium content analysis of MSCs-laden microcarriers loaded into injectable hydrogels revealed their capability of tunneling formation, vascular cell growth and osteogenic differentiation. The in vivo histology and real-time polymerase chain reaction analysis revealed that transplantation of MSC-laden microcarriers supports ectopic bone formation in the rat model. The presented approach to design bioactive microcarriers offer sustained sequential delivery of bone ECM chemical cues and offer an ideal stabilized 3D microenvironment for patient-specific cell therapy applications. The proposed methodology is readily expandable to integrate other cells and cytokines in a tuned spatiotemporal manner for personalized regenerative medicine.
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http://dx.doi.org/10.1038/s41598-020-68221-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366644PMC
July 2020

Adoptive Treg cell-based immunotherapy: Frontier therapeutic aspects in rheumatoid arthritis.

Immunotherapy 2020 08 7;12(12):933-946. Epub 2020 Jul 7.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

The major current focus on treating rheumatoid arthritis is to put an end to long-term treatments and instead, specifically block widespread immunosuppression by developing antigen-specific tolerance, while also permitting an intact immune response toward other antigens to occur. There have been promising preclinical findings regarding adoptive Treg cells immunotherapy with a critically responsible function in the prevention of autoimmunity, tissue repair and regeneration, which make them an attractive candidate to develop effective therapeutic approaches to achieve this interesting concept in many human immune-mediated diseases, such as rheumatoid arthritis. or manipulation protocols are not only utilized to correct Treg cells defect, but also to benefit from their specific immunosuppressive properties by identifying specific antigens that are expressed in the inflamedjoint. The methods able to address these deficiencies can be considered as a target for immunity interventions to restore appropriate immune function.
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http://dx.doi.org/10.2217/imt-2020-0071DOI Listing
August 2020

Burgeoning Polymer Nano Blends for Improved Controlled Drug Release: A Review.

Int J Nanomedicine 2020 19;15:4363-4392. Epub 2020 Jun 19.

School of Dentistry, Marquette University, Milwaukee, WI 53233, USA.

With continual rapid developments in the biomedical field and understanding of the important mechanisms and pharmacokinetics of biological molecules, controlled drug delivery systems (CDDSs) have been at the forefront over conventional drug delivery systems. Over the past several years, scientists have placed boundless energy and time into exploiting a wide variety of excipients, particularly diverse polymers, both natural and synthetic. More recently, the development of nano polymer blends has achieved noteworthy attention due to their amazing properties, such as biocompatibility, biodegradability and more importantly, their pivotal role in controlled and sustained drug release in vitro and in vivo. These compounds come with a number of effective benefits for improving problems of targeted or controlled drug and gene delivery systems; thus, they have been extensively used in medical and pharmaceutical applications. Additionally, they are quite attractive for wound dressings, textiles, tissue engineering, and biomedical prostheses. In this sense, some important and workable natural polymers (namely, chitosan (CS), starch and cellulose) and some applicable synthetic ones (such as poly-lactic-co-glycolic acid (PLGA), poly(lactic acid) (PLA) and poly-glycolic acid (PGA)) have played an indispensable role over the last two decades for their therapeutic effects owing to their appealing and renewable biological properties. According to our data, this is the first review article highlighting CDDSs composed of diverse natural and synthetic nano biopolymers, blended for biological purposes, mostly over the past five years; other reviews have just briefly mentioned the use of such blended polymers. We, additionally, try to make comparisons between various nano blending systems in terms of improved sustained and controlled drug release behavior.
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http://dx.doi.org/10.2147/IJN.S252237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314622PMC
August 2020

Aptamer Hybrid Nanocomplexes as Targeting Components for Antibiotic/Gene Delivery Systems and Diagnostics: A Review.

Int J Nanomedicine 2020 17;15:4237-4256. Epub 2020 Jun 17.

Marquette University School of Dentistry, Milwaukee, WI 53233, USA.

With the passage of time and more advanced societies, there is a greater emergence and incidence of disease and necessity for improved treatments. In this respect, nowadays, aptamers, with their better efficiency at diagnosing and treating diseases than antibodies, are at the center of attention. Here, in this review, we first investigate aptamer function in various fields (such as the detection and remedy of pathogens, modification of nanoparticles, antibiotic delivery and gene delivery). Then, we present aptamer-conjugated nanocomplexes as the main and efficient factor in gene delivery. Finally, we focus on the targeted co-delivery of genes and drugs by nanocomplexes, as a new exciting approach for cancer treatment in the decades ahead to meet our growing societal needs.
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http://dx.doi.org/10.2147/IJN.S248736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314593PMC
August 2020

Three-dimensional bio-printing and bone tissue engineering: technical innovations and potential applications in maxillofacial reconstructive surgery.

Maxillofac Plast Reconstr Surg 2020 Dec 3;42(1):18. Epub 2020 Jun 3.

Kingston and St George's Hospitals and St George's Medical School, London, SW17 0QT UK.

Background: Bone grafting has been considered the gold standard for hard tissue reconstructive surgery and is widely used for large mandibular defect reconstruction. However, the midface encompasses delicate structures that are surrounded by a complex bone architecture, which makes bone grafting using traditional methods very challenging. Three-dimensional (3D) bioprinting is a developing technology that is derived from the evolution of additive manufacturing. It enables precise development of a scaffold from different available biomaterials that mimic the shape, size, and dimension of a defect without relying only on the surgeon's skills and capabilities, and subsequently, may enhance surgical outcomes and, in turn, patient satisfaction and quality of life.

Review: This review summarizes different biomaterial classes that can be used in 3D bioprinters as bioinks to fabricate bone scaffolds, including polymers, bioceramics, and composites. It also describes the advantages and limitations of the three currently used 3D bioprinting technologies: inkjet bioprinting, micro-extrusion, and laser-assisted bioprinting.

Conclusions: Although 3D bioprinting technology is still in its infancy and requires further development and optimization both in biomaterials and techniques, it offers great promise and potential for facial reconstruction with improved outcome.
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http://dx.doi.org/10.1186/s40902-020-00263-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270214PMC
December 2020

Microfluidic-assisted fabrication of reverse micelle/PLGA hybrid microspheres for sustained vascular endothelial growth factor delivery.

Biotechnol Appl Biochem 2020 Jun 13. Epub 2020 Jun 13.

Marquette University School of Dentistry, Milwaukee, WI, USA.

In this study, poly (d, l-lactide-co-glycolide) (PLGA) composite microspheres containing anhydrous reverse micelle (R.M.) dipalmitoylphosphatidylcholine (DPPC) nanoparticles loaded vascular endothelial growth factor (VEGF) were produced using microfluidic platforms. The VEGF-loaded R.M. nanoparticles (VRM) were achieved by initial self-assembly and subsequent lipid inversion of the DPPC vesicles. The fabricated VRMs were encapsulated into the PLGA matrix by flow-focusing geometry microfluidic platforms. The encapsulation efficiency, in vitro release profile, and the bioactivity of the produced composite microspheres were investigated. The release study showed that VEGF was slowly released from the PLGA composite microspheres over 28 days with a reduced initial burst (18  ±  4.17% in the first 24 H). The VEGF stability during encapsulation and release period was also investigated, and the results indicated that encapsulated VEGF was well preserved. Also, the bioactivity assay of the PLGA composite microspheres on human umbilical vein endothelial cells was confirmed that the encapsulated VEGF was utterly active. The present monodisperse and controllable VEGF-loaded microspheres with reproducible manner could be widely used in tissue engineering and therapeutic applications.
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http://dx.doi.org/10.1002/bab.1971DOI Listing
June 2020

Biomedical Applications of TiO Nanostructures: Recent Advances.

Int J Nanomedicine 2020 14;15:3447-3470. Epub 2020 May 14.

Marquette University School of Dentistry, Milwaukee, WI 53233, USA.

Titanium dioxide (TiO) nanostructures are one of the most plentiful compounds that have emerged in various fields of technology such as medicine, energy and biosensing. Various TiO nanostructures (nanotubes [NTs] and nanowires) have been employed in photoelectrochemical (PEC) biosensing applications, greatly enhancing the detection of targets. TiO nanostructures, used as reinforced material or coatings for the bare surface of titanium implants, are excellent additive materials to compensate titanium implants deficiencies-like poor surface interaction with surrounding tissues-by providing nanoporous surfaces and hierarchical structures. These nanostructures can also be loaded by diversified drugs-like osteoporosis drugs, anticancer and antibiotics-and used as local drug delivery systems. Furthermore, TiO nanostructures and their derivatives are new emerging antimicrobial agents to overcome human pathogenic microorganisms. However, like all other nanomaterials, toxicity and biocompatibility of TiO nanostructures must be considered. This review highlights recent advances, along with the properties and numerous applications of TiO-based nanostructure compounds in nano biosensing, medical implants, drug delivery and antibacterial fields. Moreover, in the present study, some recent advances accomplished on the pharmaceutical applications of TiO nanostructures, as well as its toxicity and biocompatibility, are presented.
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http://dx.doi.org/10.2147/IJN.S249441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234979PMC
July 2020

Magnetic dual-template molecularly imprinted polymer based on syringe-to-syringe magnetic solid-phase microextraction for selective enrichment of p-Coumaric acid and ferulic acid from pomegranate, grape, and orange samples.

Food Chem 2020 Apr 23;325:126902. Epub 2020 Apr 23.

Marquette University School of Dentistry, Milwaukee, WI 53233, USA.

Magnetic dual-template molecularly imprinted polymer ([email protected]) was prepared to enrich and determine both p-Coumaric acid (p-CA) and ferulic acid (FA) based on syringe-to-syringe magnetic solid-phase microextraction (SS-MSPME). The obtained MDMIP was characterized and recognized, and then its adsorbing performance was studied. Based on the results, the [email protected] indicated selective recognition towards p-CA and FA with large adsorption capacity. The optimization of MDMIP-SS-MSPME conditions (pH, [email protected] mass, NaCl concentration, number of cycle, and elution volume) were conducted using the central composite design (CCD). Under the optimum conditions, an effectual and a convenient method was established to determine p-CA and FA in pomegranate, grapes, and orange samples based on SS-MSPME coupling with high-performance liquid chromatography-ultraviolet (HPLC-UV). Our developed method showed the limit of detection (LOD) of 0.08 ng mL for p-CA and 0.07 ng mL for FA. The method also indicated good linearity with R > 0.99 and good recoveries of 85.12-94.96% with RSDs ≤ 5.58% spiked at three various concentration levels in pomegranate, grapes, and orange samples.
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http://dx.doi.org/10.1016/j.foodchem.2020.126902DOI Listing
April 2020

Effect of Hypoxia Preconditioned Adipose-Derived Mesenchymal Stem Cell Conditioned Medium on Cerulein-Induced Acute Pancreatitis in Mice.

Adv Pharm Bull 2020 Jun 18;10(2):297-306. Epub 2020 Feb 18.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Acute pancreatitis (AP) is an inflammatory disorder distinguished by tissue injury and inflammation of the pancreas. Using paracrine potential of mesenchymal stem cells (MSCs) provides a useful clinical approach in treating inflammatory diseases. We investigated the therapeutic effects of adipose-derived MSC conditioned medium (CM) and hypoxia preconditioned adipose-derived MSC conditioned medium (HCM) in cerulein-induced AP in mice. AP was induced in C57BL/6 mice by intraperitoneal injection of cerulein (75 μg/ kg/h × 7 times). One hour following the last injection of cerulein, mice were treated with intraperitoneal injection of CM and HCM (500 µL/mice/30 min × 3 times). Twelve hours following the treatment, serum levels of amylase and lipase were measured. In addition, pancreas pathological changes, immunohistochemical examinations for evaluation of IL-6 expression and pancreatic myeloperoxidase (MPO) enzyme activity were analyzed. The results of the morphological, differentiation and immunophenotyping analyses confirmed that hypoxia preconditioned MSCs (HP-MSCs) conserve MSCs characteristics after preconditioning. However, HP-MSCs significantly expressed high mRNA level of hypoxia inducible factor 1-α and higher level of total protein. The findings of the current study showed that CM and HCM significantly reduced the amylase & lipase activity, the severity of pancreas tissue injury and the expression of IL-6 and MPO enzyme activity compared with the AP group. However, no significant difference between CM and HCM groups was demonstrated. Use of CM and HCM can attenuate cerulein-induced AP and decrease inflammation in the pancreas tissue in AP mice.
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http://dx.doi.org/10.34172/apb.2020.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191232PMC
June 2020